crossing96/oncoscreening huggingface dataset:
Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells.	Bladder cancer is the fourth and eighth most common cancer in men and women in the United States, respectively. Survivin, a member of inhibitor of apoptosis protein (IAP) gene family, is deregulated in a wide range of malignancies, including carcinoma of the bladder urothelium. Recent advances have identified survivin as a novel intervention target to induce apoptosis in cancer cells by phytochemicals or synthetic agents. Silibinin is a naturally occurring flavanone, isolated from milk thistle extract, and has been shown to possess cancer prevention/intervention potential against various cancers. In several animal and human studies, it is found to be safe and non-toxic. Human bladder transitional-cell papilloma RT4 cells were treated with silibinin and analyzed for survivin protein and mRNA levels by Western blotting and real-time RT-PCR, respectively. Silibinin treatment of cells for 24 h at 100 microM dose resulted in approximately 50% decrease in survivin protein level; however, treatment at 200 microM dose for 24 and 48 h showed a complete loss in survivin protein without any change in actin used as loading control. Employing RT-PCR analysis we also observed that silibinin causes a strong to complete decrease in survivin mRNA levels. In other studies, down-regulation of survivin by silibinin was associated with a very strong and prominent caspases-9 and -3 activation as well as PARP cleavage. Quantitative apoptotic assay showed that silibinin decreased survivin levels and caspases-PARP cleavages, in accord with a strong apoptotic death and growth inhibition of RT4 cells. Together, these findings suggest that more studies are needed to investigate in vivo effect of silibinin on survivin expression and associated biological effects in bladder cancer that could provide useful information for silibinin efficacy in the prevention/intervention of human bladder cancer.	bladder
High-throughput tissue microarray analysis of 11q13 gene amplification (CCND1, FGF3, FGF4, EMS1) in urinary bladder cancer.	Gene amplification is a common mechanism for oncogene overexpression. High-level amplifications at 11q13 have been repeatedly found in bladder cancer by comparative genomic hybridization (CGH) and other techniques. Putative candidate oncogenes located in this region are CCND1 (PRAD1, bcl-1), EMS1, FGF3 (Int-2), and FGF4 (hst1, hstf1). To evaluate the involvement of these genes in bladder cancer, a tissue microarray (TMA) containing 2317 samples was screened by fluorescence in situ hybridization (FISH). The frequency of gains and amplifications of all genes increased significantly from stage pTa to pT1-4 and from low to high grade. In addition, amplification was associated with patient survival and progression of pT1 tumours. Among 123 tumours with amplifications, 68.3% showed amplification of all four genes; 19.5% amplification of CCND1, FGF4, and FGF3; and 0.8% co-amplification of FGF4, FGF3, and EMS1. Amplification of CCND1 alone was found in 9% of the tumours, while EMS1 alone was amplified in 1.6% and FGF4 in 0.8%. Overall, the amplification frequency decreased with increasing genomic distance from CCND1, suggesting that, among the genes examined, CCND1 is the major target gene in the 11q13 amplicon in bladder cancer.	bladder
Inverse correlation between high level expression of cyclin E and proliferation index in transitional cell carcinoma of the bladder.	BACKGROUND/AIMS: Overexpression of the G1 cyclins, D1 and E, and/or downregulation of p27(Kip1) allow uncontrolled tumour cell proliferation. This study investigated the relation between these three cell cycle proteins and tumour proliferation in bladder cancer. METHOD: Nuclear expression of cyclin D1, cyclin E, and p27(Kip1) was determined immunohistochemically in 52 primary transitional cell carcinomas, and the Ki-67 proliferation marker was also assessed. For each protein, the percentage of positive tumour cell nuclei was determined and analysed as a continuous variable. RESULTS: Advancing tumour grade and pathological stage were accompanied by increasing proliferation indices, but decreasing p27(Kip1) and cyclin D1 expression, with no significant change in cyclin E expression. Overall, cyclin D1 and E expression did not correlate with proliferation. However, in cyclin D1 overexpressing tumours (> or = 5% nuclei positive), the level of cyclin D1 expression positively correlated with proliferation. The correlation between cyclin E expression and proliferation changed from positive to negative with increasing levels of cyclin E expression, accompanied by a coordinate increase in p27(Kip1) expression. Overall, there was an inverse association between p27(Kip1) expression and proliferation. However, a subset of tumours displayed high proliferation indices despite high p27(Kip1) expression. The G1 cyclin index (sum of the level of expression of cyclins D1 and E) correlated positively with proliferation in superficial but not muscle invasive tumours. This correlation was stronger when the G1 cyclin index was adjusted for p27(Kip1) expression. CONCLUSION: These findings support a role for these proteins in the proliferation, differentiation, and progression of bladder transitional cell carcinomas.	bladder
Laparoscopy-assisted robotic radical cystoprostatectomy with ileal conduit urinary diversion for muscle-invasive bladder cancer: initial two cases.	BACKGROUND AND PURPOSE: The use of the da Vinci robot is being investigated in the discipline of urologic surgery. We describe our experience with its use during radical cystoprostatectomy in two patients with organ-confined bladder cancer. PATIENTS AND METHODS: Laparoscopic radical cystoprostatectomy with ileal conduit urinary diversion was performed using the da Vinci robot. Both patients were informed about this new approach, and informed consent was obtained. RESULTS: There were no intraoperative or postoperative complications. The operative time was 10 and 12 hours. A clear liquid diet was started on the third postoperative day. Final histopathology examination in both patients revealed T(3a)N(0)M(0) transitional-cell carcinoma. The hospital stay was 6 days. Both patients returned to normal activity within 2 weeks. CONCLUSION: Robot-assisted laparoscopic radical cystoprostatectomy with ileal conduit urinary diversion for muscle-invasive bladder cancer is feasible.	bladder
[Bladder leiomyoma. Diagnostic and therapeutic approach].	The authors report their experience of four cases of bladder leiomyoma. Although MRI is currently the reference radiological examination, the diagnosis must be confirmed by histological examination. The various diagnostic steps and resulting therapeutic indications are described with a review of the literature.	bladder
Marginal regression of gaps between recurrent events.	Recurrent event data typically exhibit the phenomenon of intra-individual correlation, owing to not only observed covariates but also random effects. In many applications, the population may be reasonably postulated as a heterogeneous mixture of individual renewal processes, and the inference of interest is the effect of individual-level covariates. In this article, we suggest and investigate a marginal proportional hazards model for gaps between recurrent events. A connection is established between observed gap times and clustered survival data with informative cluster size. We subsequently construct a novel and general inference procedure for the latter, based on a functional formulation of standard Cox regression. Large-sample theory is established for the proposed estimators. Numerical studies demonstrate that the procedure performs well with practical sample sizes. Application to the well-known bladder tumor data is given as an illustration.	bladder
Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder.	Deletions of the long arm of chromosome 9 are the most common genetic alteration in transitional cell carcinoma (TCC) of the bladder. Several regions of deletion on 9q have been mapped by loss of heterozygosity (LOH) analysis, one of which encompasses one of the two loci for tuberous sclerosis, TSC1, at 9q34. Tuberous sclerosis complex (TSC) is an autosomal dominant condition in which affected individuals develop benign tumors (hamartomas) in many organs. There is a small increase in risk of renal cell carcinoma (<2%), but the hamartomas are of stromal origin and patients do not develop an excess of epithelial malignancies. However, during a search for candidate bladder tumor suppressor genes within the 9q34 region of LOH, we previously found a small number of mutations of TSC1, raising the possibility that this represents a bladder tumor suppressor. Here, we have carried out mutation analysis of 62 bladder tumors and 33 bladder tumor-derived cell lines to establish the frequency and spectrum of TSC1 mutations in TCC. Twelve percent of samples contained mutations. We found 10 somatic mutations, 9 of which are novel mutations not found previously in TSC cases. Two of these were missense mutations, a type of change only rarely observed in the germ line in TSC. We also identified a bladder tumor patient carrying a germ-line mutation but with no symptoms of TSC. The tumor in this case and in two other cases with somatic mutations retained the wild-type allele. Thus 3 cases with mutation retained heterozygosity for TSC1 despite our selection of tumors mostly with 9q LOH (>80%) for the study. This may indicate that haploinsufficiency for TSC1 can contribute to the development of bladder cancer and, if so, that the LOH of TSC1 observed in >50% of TCCs is biologically significant.	bladder
Near misses in bladder cancer - an airline safety approach to urology.	INTRODUCTION: Traditionally, surgical audit has identified and highlighted the incidence of adverse events complicating a patient's care. The airline industry has taken this concept a step further back by identifying and studying near misses, i.e. events that have the potential to do harm. We have applied this approach to patients with known or suspected bladder cancer. PATIENTS AND METHODS: A prospective study was performed by two urology firms on all patients with known or suspected bladder cancer over a 3-week period. Patients presented to either a central (hub) hospital, or to an associated (spoke) hospital. Four stages in bladder cancer care were considered: (i) diagnostic or check flexible cystoscopy; (ii) admission to hospital prior to TURBT; (iii) peri-operative period; and (iv) first out-patient consultation. A separate proforma, comprising various aspects of management was used for each of these stages of care. If any one criterion was not met, the episode was recorded as a near miss. Near misses were classified as due to capacity limitations in the system, clerical error, equipment failure, clinical error and patient failure. RESULTS: A total of 115 completed episodes were recorded. A near miss was recorded in 65 (56.5%) of all episodes. Capacity limitations accounted for 54%, clinical error for 23%, clerical error for 16%, patient failure for 5% and equipment failure for 2% of all recorded near misses. Of particular note is that near misses relating to diagnosis were more common at the spoke hospital, delayed referral from GPs accounted for more than 25% of clinical error, diagnosis of 5 new bladder tumours was delayed and availability of upper tract imaging was a problem at all phases of patient management. CONCLUSIONS: Near misses are very common in the management of patients with bladder cancer, and their identification should provide a useful framework for identifying potential areas for improvement in patient care.	bladder
Soluble factor from murine bladder tumor-2 cell elevates nitric oxide production in macrophages and enhances the taxol-mediated macrophage cytotoxicity on tumor cells.	The therapeutic mechanism of taxol is believed to reside primarily in its ability to stabilize microtubules and prevent cell progression through mitosis. Taxol also can activate macrophage-mediated antitumor mechanism through a nitric oxide (NO)-dependent pathway. To address whether any mechanisms account for superficial urinary bladder tumor cell killing, we evaluated the effects of taxol on the growth and viability of murine bladder tumor-2 (MBT-2) cells in vitro, both in the absence and presence of murine macrophages. In addition, we evaluated whether a soluble factor generated from MBT-2 cells could modulate the antitumor activity of the taxol-activated macrophages. Although taxol inhibited the growth of MBT-2 cells, it did not kill the tumor cells. However, preincubation of macrophages with taxol significantly decreased the viability of MBT-2 cells. Secretion of NO correlated with MBT-2 cell killing, and the activated macrophages failed to kill tumor cell targets in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of NO synthase. By the co-culture of macrophages and MBT-2 cells, untreated macrophages also released modest amount of NO and this was synergistically augmented by the treatment with taxol, indicating that MBT-2 tumor cells released some unknown factor that activated the macrophages and enhanced NO production. We named this factor the tumor-derived macrophage activating factor (TMAF). The TMAF-mediated activation of macrophages to enhance the NO production was not blocked by treatment of macrophages with oxidized low-density lipoprotein (Ox-LDL), implying that the scavenger receptor of macrophages is not involved. Sodium nitroprusside (SNP), an NO donor given to the MBT-2 cells, increased the activities of c-Jun N-terminal kinase and caspase-3 in MBT-2 cells and associated with nucleosomal fragmentation or apoptosis, whereas taxol had no direct effect on these parameters. Collectively, our results strongly suggest that taxol kills the murine bladder tumor cells through indirect activation of macrophages via NO-dependent apoptosis, instead of its better-known role as the direct antimitotic action. Our results further demonstrate that TMAF acts in synergy with taxol to activate the macrophages to elicit enhanced tumor cell killing ability.	bladder
What do I tell my patients about drinking water and the risk of bladder cancer?	Occupational exposure to arylamines, schistosomiasis, and especially smoking are well-known potential causes of bladder cancer. However, numerous individuals who are diagnosed with this cancer apparently have no known etiology. Increased consumption of a variety of fluids, including water, may significantly reduce the risk of bladder cancer by reducing the overall impact time of potential carcinogens on bladder tissue. However, the quality of drinking water could also have an impact on risk. Health care professionals could play a large role in preventing bladder cancer by providing patients with new data on the impact of water quantity and quality on risk.	bladder
Impact of primary tumour characteristics on the survival of patients with lymph node metastases in bladder cancer following radical cystectomy.	BACKGROUND AND OBJECTIVE: Patients with carcinoma urinary bladder with metastasis to the lymph nodes have been believed to have a poor prognosis. The various factors affecting survival in this subset of patients are not well understood. To analyze, these factors, we retrospectively analyzed patients who had undergone radical cystectomy at our center in the last 10 years. METHODS: From Jan. 1991 to May 2001, 158 patients underwent radical cystectomy at our center. 38 of these were found to have metastasis in the regional lymph nodes (i.e. stage D). A multivariate regression analysis was done to look for factors, which predict a better survival in this group of patients. Patients were studied for age, sex, morphology of tumour (papillary or nodular), grade of tumour, local extent of the disease (T1 T3A OR T3B), lymph nodal involvement, chemotherapy (whether received or not) and no. of TUR resection before radical cystectomy. SPSS software was used and the actuarial disease specific survival calculated for each variable. RESULTS: There were 33 males and 5 females with an age range of 34-75 years (mean 56). Overall survival was 7 months to 84 months with mean of 32 months. Patients with polypoidal disease had better survival (66 months vs 15 months). Also patients with organ-confined disease (T2, T3a) had better survival than those with perivesical spread (T3b). The mean survival in N1 and N2 disease was 36 and 10 months respectively. The benefits of adjuvant chemotherapy (methotrexate and cisplatin) could not be assessed as most of the patients received chemotherapy. CONCLUSION: Patients with positive lymph nodes for metastases have fairly good survival with radical cystectomy especially those who have a lower T stage (organ confined), papillary morphology and N1 disease.	bladder
Model-order reduction of nonlinear models of electromagnetic phased-array hyperthermia.	A method based on the Karhunen-Loéve (KL) transform is proposed for the reduction of large-scale, nonlinear ordinary differential equations such as those arising from the finite difference modeling of biological heat transfer. The method of snapshots is used to expedite computation of the required quantities in the KL procedure. Guidelines are presented and validated for snapshot selection and resultant basis series truncation, emphasizing the special physical features of the electromagnetic phased-array heat transfer physics. Applications to fast temperature prediction are presented.	bladder
Perioperative Chemotherapy in Advanced Bladder Cancer - Part II: Adjuvant Treatment.	Despite radical cystectomy, 40% of the patients with locally advanced disease and more than 80% of the patients with lymphatic metastases die tumor related. This provides the rationale for additional effective systemic therapy following surgery. In addition, previous surgery and consecutive histopathological or cell-based evaluation offers the advantage to expose only those patients to adjuvant systemic chemotherapy, who belong to a defined high-risk group. Regional lymph node metastases range from less than 10% in T1 to nearly 33% in T3/T4 lesions. Therefore, the extend of the lymph node dissection as an integral part of the surgical treatment gains importance. As pathological assessment of an adequate number of lymph nodes increases the likelihood of proper staging and decisions on further therapy depend on accurate staging, a standardization of lymphadenectomy is desirable. This paper provides an overview on the current concepts of the use of adjuvant systemic chemotherapy in the treatment of advanced urothelial cancer.	bladder
[Systemic chemotherapy for transitional cell carcinoma of the urothelium].	Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid eighties of the past century clinically significant response rates as well as prolonged survival has been documented. This review summarizes seven Phase-III trials of systemic chemotherapy for advanced urothelial carcinoma as well as results from adjuvant and neoadjuvant Phase-III trials for muscle-invasive bladder cancer including the most recent reports.	bladder
[Surgical treatment of advanced baldder carcinoma].	Radical cystectomy is the treatment of choice for patients with muscle-invasive or locally advanced bladder carcinoma. Alternative treatment options are simultaneous radiochemotherapy following transurethral tumor resection or percutaneous definitive radiotherapy. To prevent early tumor progression, treatment decision should be made within 6 months after initial diagnosis. Extended lymphadenectomy seems to have an impact on progression-free survival, as determined in retrospective analyses. Excellent long-term results exist for urinary diversion using ileal neobladder or ureter bowel implantation into an augmented colon sigmoideum segment. Similarly good results are reported for female patients. Quality of life (QoL) in correlation to type of urinary diversion is under discussion. Ileal conduit seems to be of advantage for QoL especially in elderly patients. Surgical removal of metastases is controversially discussed, especially in those patients without tumor-related symptoms. An age of more than 70 years seems to be no exclusion criterion for radical cystectomy. Treatment morbidity and mortality are similar to those of younger patients. Long-term results confirm the excellent results of orthotopic bladder replacement.	bladder
[Cases of bacillus Calmette-Guerin-induced granulomatous prostatitis and prostatic stromal invasion of the bladder carcinoma in situ, showing similar clinical findings].	Intravesical instillation of bacillus Calmette-Guerin (BCG) is the first-line therapeutic option for flat carcinoma in situ (CIS) of the bladder. Intravesical BCG instillation has been demonstrated to cause granulomatous prostatitis. Bladder CIS often also is known to show prostatic stromal invasion. We report a case of BCG-induced granulomatous prostatitis and a case of prostatic stromal invasion of bladder CIS accompanied by locally advanced prostate cancer, which showed similar clinical findings after the intravesical BCG therapy. In these 2 patients, urinary symptoms such as dysuria were prolonged regardless of anti-tuberculous medication, hard nodules were palpable at the prostate, and hypoechoic lesions were visualized by transrectal ultrasound. Both patients were treated by transurethral resection of the prostate, and the diagnoses were made by histopathological examination. Urinary symptoms were resolved in both patients after surgery, but the prostatic stromal tumor showed recurrence of growth. We report the usefulness of transurethral resection of the prostate for medication-resistant BCG-induced granulomatous prostatitis, and the importance of the correct diagnosis of prostatic stromal invasion of bladder CIS especially in the cases with concurrent prostate cancer.	bladder
Thrombotic microangiopathy and digital necrosis: two unrecognized toxicities of gemcitabine.	We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man, was given first-line metastatic treatment with gemcitabine for a adenocarcinoma of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset of subacute renal failure associated with hemolytic anemia of mechanical origin was observed. A diagnosis of probable gemcitabine-induced thrombotic microangiopathy was arrived at. Symptoms resolved after stopping the chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old man, was administered a combination of gemcitabine and a platinum salt as first-line metastatic treatment for carcinoma of the bladder urothelium. Following a cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic lesions of the finger pads that became necrotic. The work-up was negative and a causal relationship was attributed to gemcitabine. The patient made good progress when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy was withdrawn. We conclude that gemcitabine must be added to the list of drugs that cause HUS and necrotizing vasculitis.	bladder